In situ architecture of Opa1-dependent mitochondrial cristae remodeling.
In situ architecture of Opa1-dependent mitochondrial cristae remodeling.
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Opa1 依赖性线粒体嵴重塑的原位结构。
DOI：
10.1101/2023.01.16.524176
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
C
中科院分区：
文献类型：
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作者：
Fry,MichelleY;Navarro,PaulaP;Hakim,Pusparanee;Ananda,VirlyY;Qin,Xingping;Landoni,JuanC;Rath,Sneha;Inde,Zintis;Lugo,CamilaMakhlouta;Luce,BridgetE;Ge,Yifan;McDonald,JulieL;Ali,Ilzat;Ha,LeillaniL;Kleinstiver,BenjaminP;C
嵴膜状态在调节线粒体功能和细胞代谢中起核心作用。蛋白质视神经萎缩1（Opa 1）是一种重要的嵴重塑剂，在线粒体中以两种形式存在，即膜锚定长型（l-Opa 1）和加工短型（s-Opa 1）。Opa 1如何影响嵴形状的机制仍然不清楚，由于缺乏嵴的天然三维视图。我们进行原位冷冻电子断层扫描冷冻聚焦离子束研磨小鼠胚胎成纤维细胞定义Opa 1状态，以了解如何每种形式的Opa 1影响嵴结构。在我们的断层图像中，我们观察到各种各样的嵴形状，具有依赖于s-Opa 1：l-Opa 1平衡的明显趋势。增加l-Opa 1水平促进嵴堆积和延长线粒体，而增加s-Opa 1水平与不规则嵴包装和圆形线粒体形状相关。功能分析表明，在野生型细胞凋亡和钙处理反应的作用，l-Opa 1，并显示出受损的呼吸功能下Opa 1的不平衡。总之，我们提供了嵴结构的三维可视化，以揭示依赖于Opa 1介导的膜重塑的线粒体超微结构和细胞功能之间的关系。
Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to lack of native three-dimensional views of cristae. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts with defined Opa1 states to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe a variety of cristae shapes with distinct trends dependent on s-Opa1:l-Opa1 balance. Increased l-Opa1 levels promote cristae stacking and elongated mitochondria, while increased s-Opa1 levels correlated with irregular cristae packing and round mitochondria shape. Functional assays indicate a role for l-Opa1 in wild-type apoptotic and calcium handling responses, and show a compromised respiratory function under Opa1 imbalance. In summary, we provide three-dimensional visualization of cristae architecture to reveal relationships between mitochondrial ultrastructure and cellular function dependent on Opa1-mediated membrane remodeling.